1. Field of the Invention
The invention relates to the preparation of sterile, exogenous, whole saliva and a method of treating saliva deficient subjects by oral administration of this preparation.
2. Description of the Related Art
The principal protector of oral tissues is saliva produced by the salivary glands. Under some conditions, the functioning of the salivary glands becomes impaired or destroyed. Particularly devastating to the salivary glands are therapeutic irradiation used to treat head and neck cancer, and disease conditions such as AIDS, Grafts versus Host Disease (GHVD) and a wide variety of connective tissue and/or autoimmune disorders such as Sjogren's syndrome, rheumatoid arthritis, systemic lupus erythematosus and scleroderma. When the function of the salivary glands is reduced by 50% or more, individuals complain of dry mouth (xerostomia).
When the salivary glands are impaired or destroyed, serious complications follow. Included among these complications are inflammation, infection, ulceration and pain of the oral tissues. Also present are severe oral dryness, dysgeusia, dysphonia and dysphagiao These changes affect morbidity, profoundly alter the patient's quality of life, contribute to a loss of weight and often lead to significant compliance problems.
Attempts made to solve the problems related to impaired salivary glands have met with only limited success. Efforts to stimulate a patient's residual saliva producing capability depends on the presence of viable salivary gland tissue which may be non-existent or barely present.
A number of saliva substitutes are available for the treatment of xerostomia (dry mouth). Such substitutes are described, for example in U.S. Pat. Nos. 5,128,132, 4,938,963 and 4,438,100. These substitutes however, do not contain the wide array of naturally occurring proteins which are responsible for the natural protective properties of saliva.
Saliva, unlike other body fluids such as blood, contains a very high concentration of microorganisms which are indigenous or acquired oropharyngeal flora. These microorganisms should be inactivated if saliva is to be stored for any period of time. Many types of sterilization, however, damage the salivary proteins.
Whole saliva has been treated by filtration, ethylene oxide, hydrogen peroxide and gamma or ultraviolet radiation for use as a laboratory culture medium by C. J. Williams, et al., "Sterilization and Storage of Saliva" J. dent. Res 42:1416-1428 (1963), who determined that 3% ethylene oxide was effective only at 37.degree. C. This temperature alone can be damaging to the proteins. UV radiation was effective only with prefiltered saliva. However, filtration removes important proteins. The other methods excessively denatured the proteins.
More recently, saliva has been treated with dithiothreitol (DTT) and similarly sterilized by filtration or ethylene oxide treatment for use as a laboratory culture medium for oral bacteria by Kalfas and Rundegren, "Biological Quantities of Saliva Sterilized By Filtration or Ethylene Oxide Treatment", Oral Microbiol. Immunol. 6:182-186 (1991). These methods were found to cause denaturation and depolymerization of salivary proteins or to filter out protein. Moreover, the DTT is toxic to humans.
Chlorhexidine has been used as an oral rinse, see e.g., M. Addy et al., "The Effect of Some Chlorhexidine Containing Mouthrinses on Salivary Bacterial Counts," J. Clin. Peridontal. 18:90-93 (1991). There has been no suggestion to collect saliva and treat it with chlorhexidine.
Accordingly, it is an object of the invention to provide a method for sterilizing or disinfecting collected saliva while preserving its protective properties, particularly its proteins.
It is a further object of the invention to provide a method of treating persons with impaired salivary glands by administering sterilized or disinfected autologous saliva which substantially retains protective proteins.